A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

/pdf/a-default-mode-of-brain-function-zwenkbmjw7.pdf

A default mode of brain function.

Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trialby-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.

/pdf/neurophysiological-investigation-of-the-basis-of-the-fmri-1pwsdtcobg.pdf

Neurophysiological investigation of the basis of the fMRI signal

Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology.

https://www.pnas.org/content/pnas/89/12/5675.full.pdf

Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.

Functional magnetic resonance imaging (fMRI) is currently the mainstay of neuroimaging in cognitive neuroscience. Advances in scanner technology, image acquisition protocols, experimental design, and analysis methods promise to push forward fMRI from mere cartography to the true study of brain organization. However, fundamental questions concerning the interpretation of fMRI data abound, as the conclusions drawn often ignore the actual limitations of the methodology. Here I give an overview of the current state of fMRI, and draw on neuroimaging and physiological data to present the current understanding of the haemodynamic signals and the constraints they impose on neuroimaging data interpretation.

What we can do and what we cannot do with fMRI

The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.

/pdf/the-biopsychosocial-approach-to-chronic-pain-scientific-1047fjbjjh.pdf

The Biopsychosocial Approach to Chronic Pain: Scientific Advances and Future Directions

At high magnetic fields (7 and 8.4 T), water proton magnetic resonance images of brains of live mice and rats under pentobarbital anesthetization have been measured by a gradient echo pulse sequence with a spatial resolution of 65 x 65-microns pixel size and 700-microns slice thickness. The contrast in these images depicts anatomical details of the brain by numerous dark lines of various sizes. These lines are absent in the image taken by the usual spin echo sequence. They represent the blood vessels in the image slice and appear when the deoxyhemoglobin content in the red cells increases. This contrast is most pronounced in an anoxy brain but not present in a brain with diamagnetic oxy or carbon monoxide hemoglobin. The local field induced by the magnetic susceptibility change in the blood due to the paramagnetic deoxyhemoglobin causes the intra voxel dephasing of the water signals of the blood and the surrounding tissue. This oxygenation-dependent contrast is appreciable in high field images with high spatial resolution.

Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields.

Unusually high image contrast in vivo magnetic resonance imaging of the brain becomes observable at high magnetic fields when the blood oxygenation level is lowered. The cause of the contrast has been attributed to a magnetic susceptibility effect induced by paramagnetic deoxyhemoglobin in red cells. When the cylinder axis of a blood vessel is not parallel to the main magnetic field, the susceptibility difference produces varying local fields around the blood vessel. In gradient-echo images, not in spin-echo images, these local fields cause intravoxel dephasing of the water signal of the surrounding tissue. This description of the contrast enhancement has been confirmed by a series of in vitro blood sample experiments and image simulations. A predicted contrast change has been demonstrated in brain images of a mouse placed at two different orientations in the magnet. From the simulated images, the dependence of the contrast on the field strength has been estimated.

Magnetic resonance imaging of blood vessels at high fields: In vivo and in vitro measurements and image simulation

The sensitivity of magnetic resonance image signals of the brain to the change in the cerebral blood oxygenation was measured in gradient echo images of rat brains at a field strength of 7 T. The sensitivity depended on the blood vessel volume relative to the tissue volume within the image voxel, and signal intensities in the cortical area were well correlated with the change in the venous blood de-oxygenation level at the sagittal sinus. Tissue signals in the image (15 ms echo time) showed a sensitivity of 10-20% change for the full range of deoxygenation level from 0-100%. From these observations and image simulations, the extent of the signal response to some neuro-stimulation which induces an increase in regional cerebral blood flow has been estimated for 4 T field strength.

Tso-Ming Lee

Papers

Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields.

Magnetic resonance imaging of blood vessels at high fields: In vivo and in vitro measurements and image simulation

The sensitivity of magnetic resonance image signals of a rat brain to changes in the cerebral venous blood oxygenation.

Energy metabolism in rat brain in vivo studied by 31P nuclear magnetic resonance: changes during postnatal development.